Decision analysis to compare treatment strategies for Stage I/favorable histology Wilms tumor

Purpose An objective of the fifth National Wilms' Tumor Study (NWTS-5) was to evaluate the efficacy of treatment regimens for anaplastic histology Wilms' tumor (AH). Patients and Methods Prospective single-arm studies were conducted. Patients with stage I AH were treated with vincristine and dactinomycin for 18 weeks. Patients with stages II to IV diffuse AH were treated with vincristine, doxorubicin, cyclophosphamide, and etoposide for 24 weeks plus flank/abdominal radiation. Results A total of 2,596 patients with Wilms' tumor were enrolled onto NWTS-5, of whom 281 (10.8%) had AH. Four-year event-free survival (EFS) and overall survival (OS) estimates for assessable patients with stage I AH (n = 29) were 69.5% (95% CI, 46.9 to 84.0) and 82.6% (95% CI, 63.1 to 92.4). In comparison, 4-year EFS and OS estimates for patients with stage I favorable histology (FH; n = 473) were 92.4% (95% CI, 89.5 to 94.5) and 98.3% (95% CI, 96.4 to 99.2). Four-year EFS estimates for patients who underwent immediate nephrectomy with stages II (n = 23), III (n = 43), and IV (n = 15) diffuse AH were 82.6% (95% CI, 60.1 to 93.1), 64.7% (95% CI, 48.3 to 77.7), and 33.3% (95% CI, 12.2 to 56.4), respectively. OS was similar to EFS for these groups. There were no local recurrences among patients with stage II AH. Four-year EFS and OS estimates for patients with bilateral AH (n = 29) were 43.8% (95% CI, 24.2 to 61.8) and 55.2% (95% CI, 34.8 to 71.7), respectively. Conclusion The prognosis for patients with stage I AH is worse than that for patients with stage I FH. Novel treatment strategies are needed to improve outcomes for patients with AH, especially those with stage III to V disease.

Download Full-text

Randomized Comparison of Cisplatin/Vincristine/Fluorouracil and Cisplatin/Continuous Infusion Doxorubicin for Treatment of Pediatric Hepatoblastoma: A Report From the Children’s Cancer Group and the Pediatric Oncology Group

Journal of Clinical Oncology ◽

10.1200/jco.2000.18.14.2665 ◽

2000 ◽

Vol 18 (14) ◽

pp. 2665-2675 ◽

Cited By ~ 242

Author(s):

Jorge A. Ortega ◽

Edwin C. Douglass ◽

James H. Feusner ◽

Marleta Reynolds ◽

John J. Quinn ◽

...

Keyword(s):

Continuous Infusion ◽

Treatment Strategies ◽

Stage Iv ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Excellent Outcome ◽

Favorable Histology ◽

Cancer Group ◽

Initial Surgery

PURPOSE: Previous studies demonstrated that chemotherapy with either cisplatin, vincristine, and fluorouracil (regimen A) or cisplatin and continuous infusion doxorubicin (regimen B) improved survival in children with hepatoblastoma. The current trial is a randomized comparison of these two regimens. PATIENTS AND METHODS: Patients (N = 182) were enrolled onto study between August 1989 and December 1992. After initial surgery, patients with stage I–unfavorable histology (UH; n = 43), stage II (n = 7), stage III (n = 83), and stage IV (n = 40) hepatoblastoma were randomized to receive regimen A (n = 92) or regimen B (n = 81). Patients with stage I–favorable histology (FH; n = 9) were treated with four cycles of doxorubicin alone. RESULTS: There were no events among patients with stage I-FH disease. Five-year event-free survival (EFS) estimates were 57% (SD = 5%) and 69% (SD = 5%) for patients on regimens A and B, respectively (P = .09) with a relative risk of 1.54 (95% confidence interval, 0.93 to 2.5) for regimen A versus B. Toxicities were more frequent on regimen B. Patients with stage I-UH, stage II, stage III, or stage IV disease had 5-year EFS estimates of 91% (SD = 4%), 100%, 64% (SD = 5%), and 25% (SD = 7%), respectively. Outcome was similar for either regimen within disease stages. At postinduction surgery I, patients with stage III or IV disease who were found to be tumor-free had no events; those who had complete resections achieved a 5-year EFS of 83% (SD = 6%); other patients with stage III or IV disease had worse outcome. CONCLUSION: Treatment outcome was not significantly different between regimen A and regimen B. Excellent outcome was achieved for patients with stage I-UH and stage II hepatoblastoma and for subsets of patients with stage III disease. New treatment strategies are needed for the majority of patients with advanced-stage hepatoblastoma.

Download Full-text

Treatment outcomes in patients less than 2 years of age with small, stage I, favorable-histology Wilms' tumors: a report from the National Wilms' Tumor Study.

Journal of Clinical Oncology ◽

10.1200/jco.1993.11.1.91 ◽

1993 ◽

Vol 11 (1) ◽

pp. 91-95 ◽

Cited By ~ 52

Author(s):

D M Green ◽

N E Breslow ◽

J B Beckwith ◽

J Takashima ◽

P Kelalis ◽

...

Keyword(s):

Wilms Tumor ◽

Stage I ◽

P Value ◽

Relapse Free Survival ◽

Free Survival ◽

Treatment Regimens ◽

Survival Percentage ◽

Favorable Histology ◽

Specimen Weight ◽

Tumor Studies

PURPOSE Retrospective analyses were performed to determine the effect of tumor weight and therapy modifications on outcome in patients less than 2 years of age with stage I favorable-histology Wilms' tumors. PATIENTS AND METHODS The 4-year relapse-free and overall survival percentages for patients randomized to different treatment regimens in National Wilms' Tumor Studies (NWTS)-1, -2, and -3 were calculated and compared. RESULTS The 4-year relapse-free survival percentages of patients whose specimen weight was less than 550 g were found to be 89.1% on NWTS-1, 96.0% on NWTS-2, and 93.2% on NWTS-3. There was no evidence that the relapse-free survival of these patients had improved over time (P value for trend = .99). The 4-year relapse-free survival percentage for similar age and stage patients whose specimen weight was 550 g or greater was significantly poorer than that of patients with smaller tumors (P = .02). CONCLUSION Changes in the NWTS treatment regimens over a period of more than 20 years have not improved on the excellent prognosis of patients who are less than 2 years of age at diagnosis and who have a stage I, favorable-histology Wilms' tumor with specimen weight less than 550 g. These data could be used as the basis for a future trial in which a subgroup of such patients is treated with nephrectomy only.

Download Full-text

Treatment outcomes in patients less than two years of age with small, stage I, favorable-histology Wilms' tumors: A report from the national Wilms' tumor study

Journal of Pediatric Surgery ◽

10.1016/0022-3468(93)90476-2 ◽

1993 ◽

Vol 28 (11) ◽

pp. 1515

Author(s):

Michael P. Hirsh

Keyword(s):

Treatment Outcomes ◽

Wilms Tumor ◽

Stage I ◽

Favorable Histology ◽

Tumor Study

Download Full-text

Augmentation of Therapy for Combined Loss of Heterozygosity 1p and 16q in Favorable Histology Wilms Tumor: A Children’s Oncology Group AREN0532 and AREN0533 Study Report

Journal of Clinical Oncology ◽

10.1200/jco.18.01972 ◽

2019 ◽

Vol 37 (30) ◽

pp. 2769-2777 ◽

Cited By ~ 6

Author(s):

David B. Dix ◽

Conrad V. Fernandez ◽

Yueh-Yun Chi ◽

Elizabeth A. Mullen ◽

James I. Geller ◽

...

Keyword(s):

Overall Survival ◽

Radiation Therapy ◽

Loss Of Heterozygosity ◽

Wilms Tumor ◽

Adverse Outcomes ◽

Stage I ◽

Stage Iii ◽

Rank Test ◽

Favorable Histology ◽

Grade 3

PURPOSE In National Wilms Tumor Study 5 (NWTS-5), tumor-specific combined loss of heterozygosity of chromosomes 1p and 16q (LOH1p/16q) was associated with adverse outcomes in patients with favorable histology Wilms tumor. The AREN0533/AREN0532 studies assessed whether augmenting therapy improved event-free survival (EFS) for these patients. Patients with stage I/II disease received regimen DD4A (vincristine, dactinomycin and doxorubicin) but no radiation therapy. Patients with stage III/IV disease received regimen M (vincristine, dactinomycin, and doxorubicin alternating with cyclophosphamide and etoposide) and radiation therapy. METHODS Patients were enrolled through the AREN03B2 Biology study between October 2006 and October 2013; all underwent central review of pathology, surgical reports, and imaging. Tumors were evaluated for LOH1p/16q by microsatellite testing. EFS and overall survival were compared using the log-rank test between NWTS-5 and current studies. RESULTS LOH1p/16q was detected in 49 of 1,147 evaluable patients with stage I/II disease (4.27%) enrolled in AREN03B2; 32 enrolled in AREN0532. LOH1p/16q was detected in 82 of 1,364 evaluable patients with stage III/IV disease (6.01%) in AREN03B2; 51 enrolled in AREN0533. Median follow-up for 83 eligible patients enrolled in AREN0532/0533 was 5.73 years (range, 2.84 to 9.63 years). The 4-year EFS for patients with stage I/II and stage III/IV disease with LOH1p/16 was 87.3% (95% CI, 75.1% to 99.5%) and 90.2% (95% CI, 81.8% to 98.6%), respectively. These results are improved compared with the NWTS-5 updated 4-year EFS of 68.8% for patients with stage I/II disease ( P = .042), and 61.3% for patients with stage III/IV disease ( P = .001), with trends toward improved 4-year overall survival. The most common grade 3 or higher nonhematologic toxicities with regimen M were febrile neutropenia (39.2%) and infections (21.6%). CONCLUSION Augmentation of therapy improved EFS for patients with favorable histology Wilms tumor and LOH1p/16q compared with the historical NWTS-5 comparison group, with an expected toxicity profile.

Download Full-text

Older Age Is an Adverse Prognostic Factor in Stage I, Favorable Histology Wilms’ Tumor Treated With Vincristine Monochemotherapy: A Study by the United Kingdom Children’s Cancer Study Group, Wilm’s Tumor Working Group

Journal of Clinical Oncology ◽

10.1200/jco.2003.01.062 ◽

2003 ◽

Vol 21 (17) ◽

pp. 3269-3275 ◽

Cited By ~ 75

Author(s):

K. Pritchard-Jones ◽

A. Kelsey ◽

G. Vujanic ◽

J. Imeson ◽

C. Hutton ◽

...

Keyword(s):

United Kingdom ◽

Prognostic Factor ◽

Wilms Tumor ◽

Stage I ◽

Study Group ◽

Cancer Study ◽

Adverse Prognostic Factor ◽

Favorable Histology ◽

The United Kingdom ◽

Cancer Study Group

Purpose: To identify clinical prognostic factors in children with stage I, favorable histology (FH) Wilms’ tumor treated with vincristine monochemotherapy after immediate nephrectomy to define subgroups for consideration of further reduction in treatment intensity. Patients and Methods: During two consecutive trials of the United Kingdom Children’s Cancer Study Group (UKW2 and UKW3, 1986 to 2001), 242 children with stage I FH Wilms’ tumor were treated with immediate nephrectomy followed by 10 weekly injections of vincristine 1.5 mg/m2. Event-free survival (EFS) and overall survival (OS) were compared by age group. Results: The 4-year EFS rate was 93.2%, 87.2%, and 71.3% for children less than 2 years old, 2 to 4 years old, and 4 years old or older at diagnosis, respectively (log-rank, P = .001); the corresponding 4-year OS rate was 98.1%, 95.0%, and 87.2% (log-rank, P = .01). There were no toxicity- or procedure-related deaths. In multivariate analysis, specimen weight was not of independent prognostic value (P = .66). Among the 186 children younger than 4 years at diagnosis, there were 17 relapses and five deaths, compared with 16 relapses and eight deaths among the 56 children at least 4 years old at diagnosis. OS after relapse was surprisingly poor (61.6% at 4 years). Conclusion: Treatment for stage I FH Wilms’ tumor is generally successful using vincristine monotherapy after immediate nephrectomy, and therefore, the risks of dactinomycin hepatopathy can be avoided. However, age at least 4 years is a significant adverse prognostic factor. This treatment schedule should be considered in any trial of treatment reduction in very young children with stage I FH Wilms’ tumor, regardless of tumor size, and we suggest that the upper age limit for the reduced therapy be set at 4 years.

Download Full-text

Pulmonary metastases after nephrectomy only for small, stage I/favorable-histology Wilms’ tumor

Pediatric Surgery International ◽

10.1007/s00383-005-1418-5 ◽

2005 ◽

Vol 21 (6) ◽

pp. 470-473

Author(s):

Toshiji Shitara ◽

Yoshiaki Tsuchida ◽

Junko Hirato ◽

Akira Shimada ◽

Hideaki Murai ◽

...

Keyword(s):

Pulmonary Metastases ◽

Wilms Tumor ◽

Stage I ◽

Favorable Histology

Download Full-text

Prognostic factors for children with recurrent Wilms' tumor: results from the Second and Third National Wilms' Tumor Study.

Journal of Clinical Oncology ◽

10.1200/jco.1989.7.5.638 ◽

1989 ◽

Vol 7 (5) ◽

pp. 638-647 ◽

Cited By ~ 122

Author(s):

P Grundy ◽

N Breslow ◽

D M Green ◽

K Sharples ◽

A Evans ◽

...

Keyword(s):

Prognostic Factors ◽

Wilms Tumor ◽

Survival Rates ◽

Initial Therapy ◽

Chemotherapeutic Agents ◽

Stage I ◽

Prognostic Features ◽

Favorable Histology ◽

Tumor Study ◽

Unilateral Disease

The characteristics of 367 stage I-IV National Wilms' Tumor Study (NWTS) children who relapsed after initial treatment for unilateral disease in the second and third NWTS trials (NWTS-2 and -3) were analyzed to identify features predictive of survival. Although modifications in initial therapy resulted in a lower rate of first relapse in these two studies compared with NWTS-1, all previously identified prognostic factors after relapse remained statistically significant predictors of survival. Tumor histology, length of initial remission, initial therapy with two v three drugs, and site of relapse each were independently predictive of postrelapse survival. The 3-year postrelapse survival for all 367 patients was 30% +/- 3%; however, subgroups classified by these prognostic factors were identified that had 3-year postrelapse survival rates of greater than 40%. These subgroups included patients who had tumors of favorable histology (FH) that recurred (1) only in the lungs, (2) in the abdomen when radiotherapy (RT) was not initially given, or (3) that were originally stage I, (4) that were originally treated with only two drugs, or (5) that recurred 12 months or more after diagnosis. These results were achieved with the use of standard treatments, ie, surgery, RT, and chemotherapy using dactinomycin (AMD), vincristine (VCR), and Adriamycin [( ADR] doxorubicin; Adria Laboratories, Columbus, OH). It is suggested that patients in these groups might be managed with aggressive use of conventional therapies until newer chemotherapeutic agents and drug combinations are shown to be more effective. Patients with adverse prognostic features at relapse have a poor survival expectancy with standard measures. Salvage attempts for these patients are better based on experimental approaches.

Download Full-text